Disruption of Type I Interferon Induction by a KSHV Homologue of IPS-1

项目摘要 疱疹感染是世界上最常见的病毒感染之一。这些病毒 可以是亚临床的，或者在卡波西肉瘤相关疱疹病毒（KSHV）的情况下，它们可以导致 危险的疾病，如癌症。众所周知，KSHV在艾滋病患者中引起卡波西肉瘤（KS） 和其他几种淋巴增生性疾病。众所周知，I型干扰素是人体的天然抗- 病毒系统和几乎所有导致人类感染的病毒都有办法阻止或利用这种病毒， 系统来增强其在主机中的复制。我们在KSHV基因组中发现了一个新的ORF， 似乎是IPS 1蛋白的病毒同源物，IPS 1蛋白是I型干扰素诱导途径的关键衔接子。 该蛋白在KSHV裂解病毒复制期间高度表达。此应用程序的总体目标是 确定KSHV如何使用这种新的病毒蛋白来操纵先天免疫系统， 通常限制KSHV复制。在第一个具体目标中，我们将重点确定KSHV如何使用此 基因干扰干扰素以及复制有效。在第二个目标中，我们计划确定以下方面的重要性： 这种新的基因的构建和表征的KSHV缺陷的这种病毒同系物的IPS 1。 这个项目的长期目标是确定KSHV免疫调节如何发生在阻断的目标 这种操纵和限制KSHV复制。

Project Abstract Herpes infections represent one of the most common viral infections that exists in the world. These viruses can be subclinical or as in the case of Kaposi’s Sarcoma Associated Herpesvirus (KSHV) they can lead to dangerous diseases such as cancer. KSHV is well known in AIDS patients to cause Kaposi’s Sarcoma (KS) and several other lymphoproliferartive diseases. Type I Interferon is well known to be the body’s natural anti- viral system and almost all viruses that cause infection in humans have devolved ways to block or use this system to enhance their replication in the host. We have found a novel ORF within the genome of KSHV that seems to be a viral homologue of the IPS1 protein, a critical adaptor of the Type I Interferon induction pathway. This protein is highly expressed during KSHV lytic viral replication. The overall goal of this application is to determine how KSHV uses this novel viral protein to manipulate the innate immune system that should normally limit KSHV replication. In the first specific aim, we will focus on determining how KSHV uses this gene to disrupt IFN as well as replicate efficiently. In the second aim, we plan to determine the importance of this novel gene by the construction and characterization of a KSHV deficient in this viral homologue of IPS1. The long-term goal of this project is to determine how KSHV immune modulation occurs in the goal of blocking this manipulation and limiting KSHV replication.